The Gβγ Dimer Drives the Interaction of Heterotrimeric Gi Proteins with Nonlamellar Membrane Structures*
The Gβγ Dimer Drives the Interaction of Heterotrimeric Gi Proteins with Nonlamellar Membrane Structures*
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DOI：
10.1074/jbc.m402061200
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发表时间：
2004-08
影响因子：
4.8
通讯作者：
Oliver Vögler;J. Casas;Danita Capó;T. Nagy;G. Borchert;G. Martorell;P. Escribá
中科院分区：
文献类型：
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作者：
Oliver Vögler;J. Casas;Danita Capó;T. Nagy;G. Borchert;G. Martorell;P. Escribá
异源三聚体G蛋白是外周膜蛋白，其将信号从膜受体传播到位于不同细胞区室中的调节蛋白。为了促进信号放大，G蛋白相对于G蛋白偶联受体摩尔过量。由于G蛋白能够从细胞膜转移到胞质溶胶，因此蛋白质-脂质相互作用在信号转导中起着至关重要的作用。在这里，我们研究了异源三聚体G蛋白（G α β γ）与模型膜（脂质体）的结合以及受体介导的激活后形成的实体（G α和G β γ）的结合。所使用的模型膜由能够组织成层状或非层状（六边形HII）膜结构的确定的膜脂质组成。我们证明，尽管异源三聚体Gi蛋白和G β γ二聚体可以与磷脂酰胆碱的脂质双层结合，但磷脂酰乙醇胺的非层状相的存在显著增强了它们与膜的结合。相反，活化的G蛋白α亚基表现出相反的膜结合行为，明显偏好于层状膜。这些结果对细胞信号传导有重要影响。首先，G β γ二聚体的结合特性解释了异源三聚体G蛋白的脂质结合行为和细胞定位。第二，异源三聚体G蛋白、G β γ二聚体和G α亚基与膜脂质的不同蛋白-脂质相互作用部分解释了它们在受体激活后的信号传导过程中的不同细胞动员。最后，它们与脂质的差异相互作用表明膜脂质二级结构在通过G蛋白偶联受体传播信号中的积极作用。
Heterotrimeric G proteins are peripheral membrane proteins that propagate signals from membrane receptors to regulatory proteins localized in distinct cellular compartments. To facilitate signal amplification, G proteins are in molar excess with respect to G protein-coupled receptors. Because G proteins are capable of translocating from membrane to cytosol, protein-lipid interactions play a crucial role in signal transduction. Here, we studied the binding of heterotrimeric G proteins (Gαβγ) to model membranes (liposomes) and that of the entities formed upon receptor-mediated activation (Gα and Gβγ). The model membranes used were composed of defined membrane lipids capable of organizing into either lamellar or nonlamellar (hexagonal HII) membrane structures. We demonstrated that although heterotrimeric Gi proteins and Gβγ dimers can bind to lipid bilayers of phosphatidylcholine, their binding to membranes was markedly and significantly enhanced by the presence of nonlamellar phases of phosphatidylethanolamine. Conversely, activated G protein α subunits showed an opposite membrane binding behavior with a marked preference for lamellar membranes. These results have important consequences in cell signaling. First, the binding characteristics of the Gβγ dimer account for the lipid binding behavior and the cellular localization of heterotrimeric G proteins. Second, the distinct protein-lipid interactions of heterotrimeric G proteins, Gβγ dimers, and Gα subunits with membrane lipids explain, in part, their different cellular mobilizations during signaling upon receptor activation. Finally, their differential interactions with lipids suggest an active role of the membrane lipid secondary structure in the propagation of signals through G protein-coupled receptors.